Identifying Differing Intracellular Cargo Release Mechanisms by Monitoring In Vitro Drug Delivery from MOFs in Real Time

Panagiota Markopoulou; Nikolaos Panagiotou; Aurelia Li; Rocio Bueno-Perez; David Madden; Sarah Buchanan; David Fairen-Jimenez; Paul G Shiels; Ross S Forgan

doi:10.1016/j.xcrp.2020.100254

Identifying Differing Intracellular Cargo Release Mechanisms by Monitoring In Vitro Drug Delivery from MOFs in Real Time

Cell Rep Phys Sci. 2020 Nov 18;1(11):100254. doi: 10.1016/j.xcrp.2020.100254.

Authors

Panagiota Markopoulou¹, Nikolaos Panagiotou^{1

2}, Aurelia Li³, Rocio Bueno-Perez³, David Madden³, Sarah Buchanan², David Fairen-Jimenez³, Paul G Shiels², Ross S Forgan¹

Affiliations

¹ Joseph Black Building, College of Science and Engineering, School of Chemistry, University of Glasgow, Glasgow G12 8QQ, UK.
² Wolfson Wohl Cancer Research Centre, College of Medical, Veterinary, & Life Sciences, Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1QH, UK.
³ Adsorption & Advanced Materials Laboratory, Department of Chemical Engineering & Biotechnology, University of Cambridge, Cambridge CB3 0AS, UK.

Abstract

Metal-organic frameworks (MOFs) have been proposed as biocompatible candidates for the targeted intracellular delivery of chemotherapeutic payloads, but the site of drug loading and subsequent effect on intracellular release is often overlooked. Here, we analyze doxorubicin delivery to cancer cells by MIL-101(Cr) and UiO-66 in real time. Having experimentally and computationally verified that doxorubicin is pore loaded in MIL-101(Cr) and surface loaded on UiO-66, different time-dependent cytotoxicity profiles are observed by real-time cell analysis and confocal microscopy. The attenuated release of aggregated doxorubicin from the surface of Dox@UiO-66 results in a 12 to 16 h induction of cytotoxicity, while rapid release of pore-dispersed doxorubicin from Dox@MIL-101(Cr) leads to significantly higher intranuclear localization and rapid cell death. In verifying real-time cell analysis as a versatile tool to assess biocompatibility and drug delivery, we show that the localization of drugs in (or on) MOF nanoparticles controls delivery profiles and is key to understanding in vitro modes of action.

Keywords: anticancer; doxorubicin; drug delivery; in vitro; metal-organic frameworks; nanomedicine; real-time cell analysis.